Site-selective coupling of remote C(sp 3 )-H/ meta -C(sp 2 )-H bonds enabled by Ru/photoredox dual catalysis and mechanistic studies.

Construction of C(sp 2 )-C(sp 3 ) bonds via regioselective coupling of C(sp 2 )-H/C(sp 3 )-H bonds is challenging due to the low reactivity and regioselectivity of C-H bonds. Here, a novel photoinduced Ru/photocatalyst-cocatalyzed regioselective cross-dehydrogenative coupling of dual remote C-H bonds, including inert γ-C(sp 3 )-H bonds in amides and meta -C(sp 2 )-H bonds in arenes, to construct meta -alkylated arenes has been accomplished. This metallaphotoredox-enabled site-selective coupling between remote inert C(sp 3 )-H bonds and meta -C(sp 2 )-H bonds is characterized by its unique site-selectivity, redox-neutral conditions, broad substrate scope and wide use of late-stage functionalization of bioactive molecules. Moreover, this reaction represents a novel case of regioselective cross-dehydrogenative coupling of unactivated alkanes and arenes via a new catalytic process and provides a new strategy for meta -functionalized arenes under mild reaction conditions. Density functional theory (DFT) calculations and control experiments explained the site-selectivity and the detailed mechanism of this reaction.